CN1128365C - Method and apparatus for making quantitave measurements of localized accumulations of magnetic particles - Google Patents
Method and apparatus for making quantitave measurements of localized accumulations of magnetic particles Download PDFInfo
- Publication number
- CN1128365C CN1128365C CN98811381A CN98811381A CN1128365C CN 1128365 C CN1128365 C CN 1128365C CN 98811381 A CN98811381 A CN 98811381A CN 98811381 A CN98811381 A CN 98811381A CN 1128365 C CN1128365 C CN 1128365C
- Authority
- CN
- China
- Prior art keywords
- magnetic
- sample
- magnetic field
- signal
- sensing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y25/00—Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/72—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables
- G01N27/74—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables of fluids
- G01N27/745—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables of fluids for detecting magnetic beads used in biochemical assays
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/0098—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation
Landscapes
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nanotechnology (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- Hematology (AREA)
- Electrochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Investigating Or Analyzing Materials By The Use Of Magnetic Means (AREA)
- Measuring Magnetic Variables (AREA)
Abstract
The present invention relates to an apparatus for quantitatively measuring groups of magnetic particles. The particles are complexed with substances to be determined and are excited in a magnetic field. The magnetic particles (11) are thereby caused to oscillate at the excitation frequency in the manner of a dipole to create their own fields. These fields are inductively coupled to sensing coils (43) fabricated in a gradiometer configuration. The output signals from the sensing coils are appropriately amplified and processed to provide useful output indications.
Description
The technical field of the invention
The present invention relates to detect the existence of magnetic particle, relate in particular to by the method for AC excitation with the magnetic torque amplitude of the vibration of the induction detection particulate that excitation frequency caused, the accumulation that comes these magnetic particles of detection by quantitative.
Background technology
People are for determining whether particulate exists the technology of the concentration level that may reach with particulate to give sizable concern in bigger mixed liquor that contains micro particles or solution.Under some environment, people wish to measure certain organic compound with extremely low concentration.Such as, in medical science, the concentration of determining given types of molecules is very useful, these molecules usually in solution, or with the physiological fluid form of nature (such as, blood or urine) exist, be directed in the life system (such as, medicine or pollutant).
A widely used existence whether method (being referred to as analysis) that is used to detect the compound particulate of being concerned about is an immunoassay.In the method, the detection to given molecular species (being called ligand) need realize that anti-ligand or acceptor must be attached on first kind of relevant compound specially by using second kind of molecular species (being called anti-ligand or acceptor).Whether detect ligand exists and is by direct or indirect detection or infers that incorporation range between ligand and the anti-ligand is realized.
At United States Patent (USP) 4,537, among 861 (the Elings et al.) several detections and measuring method have been discussed.This patent description severally be used for finishing the methods of same para-immunity that between ligand and anti-ligand, have in conjunction with in the solution of (binding) reaction, typical ligand and anti-ligand are antigen and antibody.The document creation of Elings a spatial model, this pattern is formed by the space array of the separated region of anti-ligand material and ligand material, these dispersion of materials distribute, interact with the separated region space array of anti-ligand material, at the association reaction of spatial model, the compound of this combination is marked with specific physical features between generation ligand and the anti-ligand.When in spatial model, accumulating, can provide the immunoassays of expection when underlined by scanister in conjunction with compound.Scanister can be based on fluorescence, optical density, and light disperses, color and reflectance or the like.
According to Elings, by applying the solution of local magnetic field to coupling (bind) compound that the band magnetic particle is arranged, markd coupling compound is built up on specially prepd surface or optical transparency conduit or container.The magnitude range of magnetic particle is 0.01 to 50 micron.In case coupling compound magnetic in solution is assembled, and just can adopt previously described scanning technique.
Magnetic particle and inertia matrix material that magnetic iron ore forms are used to biochemical field for a long time.Their diameter scope to several microns, contains the scope from 15% to 100% of magnetic iron ore from several nanometers.They were described to the paramagnetic iron particulate usually, if magnitude range is bigger, just were called magnetic bead.Usual way is to coat some bioactive materials on the surface of these particulates, and these materials will cause them to combine closely with relevant specific small material or particulate (such as protein, virus, cell, dna fragmentation).These particulates just become " handle " that can come mobile object or immune object by magnetic field, and magnetic field provides with powerful permanent magnet usually.The patent of Elings is to use magnetic particle to do an example of label.Commercial can obtain to finish this target with rare-earth magnet or the specially-made product of pole piece.
Although these magnetic particles only are used to move in practice or the immune object that is coupled, people have done some experimental work, use particulate to do the existence that label detects coupled object.Label adopts radioactivity, fluorescence or phosphorescent molecules usually to the object of being concerned about.If can detect under enough little quantity, magnetic label is a kind of very attracting technology so, because other label technique all has various serious weakness.Radiometric method produces health problem and handling problem, and slow relatively.Fluorescence or phosphorescence technology are having limitation aspect quantified precision and the dynamic range, because the photon of emission is by other absorbed in the sample.Referring to Jap.P. publication 63-90765, published on April 21st, 1988 (Fujiwara et al.).
Because the signal from the magnetic particle of very small capacity is very faint, the detecting device of just attempting to set up based superconductive quantum interference device (SQUIDs) that the researchist is very natural.The superconducting quantum interference device amplifier is well-known the most responsive detector for magnetic field under many situations.But, use this method that some concrete difficulties are arranged.Because the pick-up winding of superconducting quantum interference device must maintain cryogenic temperature, so must being cooled, sample obtains maximum coupling with these coils.This process causes detecting the tedium that becomes and be difficult to accept.The complicacy of superconducting quantum interference device itself and cryogenics assembly cause it to be difficult to use as cheap desktop instrument.Even the design based on " high-tech " superconductor can not overcome these obstructions fully, but also can introduce some new difficulties (Fugiwara et al.).
Also have more classic method to detect and quantize magnetic particle.These methods relate to the magnetometer of a definite form, and sample is placed in the high-intensity magnetic field and the test sample stressing conditions, normally detect the tangible gravity change of sample when Strength Changes.An example of this technology is shown in Rohr patent 5,445,970 and 5,445,971.More complicated technology is the influence of detection of particles to milli machine cantilever deflection or vibration.(Baselt et al., " based on the biology sensor of power microtechnic ", Naval Research Labratory, J.Vac, Science Tech.B.Vol 14, No.2 (5pp) (in April, 1996)).These methods all have limitation, because they depend on intrinsic magnetic effect are converted to mechanical response.These responses must with the mechanical effect of a large amount of other type as vibrations, viscosity and buoyancy etc. differentiates.
Desktop instrument cheapness, room temperature that can directly detect and quantize very small amount of magnetic particle will have crucial application.
The present invention describes
Generally speaking, the invention provides the very little accumulation magnetic particle (such as magnetic iron ore) of a kind of direct detection and measurement and the method and apparatus of the related substances that they were coupled.
By adopting magnetic particle to come the device of detection by quantitative target particulate to form, magnetic particle and target particulate combine formation magnetic coupling composite sample in essence in the present invention, and described device comprises: the movable pedestal that has the sample of depositing by the pattern that limits; Apply the magnetic conductor of variable magnetic field to sample; The magnetic field sensing element that the output signal conductor is arranged; Move described sample and the bear results device of output signal of operative relationship is arranged to magnetic field and with described sensing element; The signal processor that comprises processor and analysis element, this signal processor is changed described output signal from described sensing element signal indication to the quantity of the sample of certain pattern is provided; And change the device of described quantity indicator signal for the useful form of people.
Magnetic particle or magnetic bead utilize known method to be coupled to the target particulate, thereby magnetic sample element or magnetic coupling compound are provided.One of the magnetic sample element limits clear and definite pattern is to deposit on flat base, and the magnetic particle in the sample is encouraged in the magnetic field that applies high amplitude high frequencies then.This causes magnetic particle to vibrate with excitation frequency as the magnetic pole of localization.From the magnetic field and induction sensing coil close-coupled of sample, sensing coil is made the gradiometer structure.This structure makes sensing coil encourage the big and consistent magnetic field of sample as far as possible farthest insensitive to being used to.And the geometric configuration of coil is designed to and the spatial model of sample coupling, changes significantly bigger response so that provide with the relative position of coil per sample.The induced voltage of process sensing coil is carefully amplified and is detected processing by phase sensitive.From the inductive pick-up of driving magnetic field reference signal itself as phase detector circuit.The output of phase detectors is by further filtering, digitizing then.
Come the modulation signal amplitude by relative sensing coil array mobile example.This allows people only because coil unbalanced, the inconsistency of driving magnetic field, and the intersection of circuit, or any other is not to refuse signal from the tangible signal source of sample itself.The deltoid that is digitized into to the relative sample position of signal amplitude compares with the theoretical response curve that uses suitable curve fitting technique to obtain.This provides the point-device magnetic sample content on intrinsic noise of instrument and skew basis to estimate.
Summary of drawings
In conjunction with the accompanying drawings, by following detailed, it is clearer that purpose of the present invention, advantage and feature can seem.Description of drawings is as follows:
Fig. 1 is the skeleton view of desktop version of the present invention.
Fig. 2 is the amplification view of the sensing coil embodiment of the present invention among Fig. 1.
Fig. 3 is the of the present invention mechanical perspective illustration of Fig. 1.
Fig. 4 is the electronics schematic block diagram of the present invention of Fig. 1.
Fig. 4 A is the planimetric map of the amplification of the base of placement sensing coil among Fig. 1.
Fig. 4 B is the skeleton view of base connector metal shell.
Fig. 5 is the amplification view of another embodiment of Fig. 1 sensing coil of the present invention.
Fig. 6 is the waveform of sensing coil output signal when the material that will measure passes sensing coil.
Preferred embodiment
With reference to the accompanying drawings, especially Fig. 1 to 3 illustrates the preferred embodiments of the present invention.
Read module
Read module and comprise several different subsystems, they are that the sample that has base moves control, and resident on this base have for the magnetic coupling composite sample that detects, and this sample moves the relative motion that control is provided at necessity in the system; Magnetic conductor, this magnetic conductor is applied to sample with pumping signal; Sensing coil, it picks up the signal that sample produces as signal pickup device; Driving circuit is for the magnetic conductor coil provides drive current; Amplifier/phase detectors/Aristogrid are used to be coupled to sensing coil and accept and handle output signal; Microprocessor chip, externally PC (PC) and read two-way communication is provided between the module.
A. sample motion control
By classic method magnetic particle is coupled to the target particulate and creates the magnetic coupling composite sample.The target particulate can comprise atom, individual molecule and biological cell etc.The accumulation of magnetic coupling composite sample is several to a hundreds of particulate, and in precalculated position 11 precipitations near base or disk 12 (Fig. 3).Form the method for coupling compound and be the method that they append to the precalculated position of disk well-known, can adopt standard technique.Disk is assembled on the axle 13 and extends downwardly into zigzag wheel disc 14.Suitable whirligig, such as stepping motor 16, have the axle 17 at its distal extension to Worm-gear assembly 15.Motor is followed the tracks of rotatablely moving of signal controlling disk 12 that PC66 applies by circuit 18.Certainly, if desired, also can adopt wireless device be coupled PC and system of the present invention.
In a preferred embodiment, as present consideration, about 47 millimeters of the diameter of disk 12, about 0.25 millimeter of thickness.Can use glass, plastics or silicon etc. to make disk.For practical purpose, its thickness range approximately is 0.1 millimeter to 1.0 millimeters.In the example of Ben Teding, wheel disc 14 is connected with disk 12 by axle 13, and the worm gear reducer device that is passed through 120 teeth by motor 16 rotates.Certainly, can adopt various rotating driving device.
Magnetic conductor 21 with respect to disk 12 linear moving, has the screw 23 of every circulation 40 commentaries on classics by whirligig (such as stepping motor 22) on the axle 24 of this motor.Axle sleeve 25 disposes the hole of internal whorl, and its screw thread matches with the spiral guiding screw flight.Control signal slave microcomputer 65 is applied to motor 22 by circuit 26.Same, the concrete condition that the rotation of explanation herein drives is an example, also can adopt other that suitable element of different characteristic is arranged.
B. magnetic conductor
In a preferred embodiment, the ring-like magnetic core 31 of ferrite (Fig. 4) has the breach 32 of about 1.5 mm wides.This core diameter is about 30 millimeters in the embodiment that describes.Drive coil 33 is wound in an individual layer, covers the scope of 270 degree of ring type magnetic core 31, the relative breach symmetry of coil.Backfeed loop 34 is wrapped on the ring-like iron core, and its position is in the position (relative with breach) of about 180 degree of breach.Loop 34 can be the outside of coil 33 or between coil 33 and ring type magnetic core.According to necessary and suitable feedback function, it can be made up of several perhaps multi-turns.The purpose of backfeed loop is sensing or the magnetic field of expressing breach 32, makes signal Processing or the output circuit can self-correcting to phenomenons such as temperature drifts.This is used to strengthen precision, is not necessity operation of native system.Ring-like magnetic conductor array unshakable in one's determination is assemblied in insulator inner room 35, and the latter can form with optical fiber glass.Inner room 35 has the groove 36 (Fig. 4) of the position of corresponding breach 32.This groove/breach moulding also is configured, and comes selectivity to accept the edge of rotatable circular disc 12, and provides the space to the sensing coil base, will describe in detail below.
C. sensing coil
Now with particular reference to Fig. 2,4, and 4A, insulator mount 41 is assembled in the groove 36 of inner room 35, and extends to breach 32.Provide coupling liner 40,42 at a nearest end, sensing coil 43 is assembled on the base that closes on tip.The most handy quartz of base or silicon are made, and sensing element is a film fine copper wire circle.Can use standard fine film manufacturing technology to construct base and sensing coil, enter with the conductor that leaves each coil on two different levels.Such as; can be placed on susceptor surface entering trace 49 by the photomechanical printing slabstone disposal route of standard; the quartz that one deck is dispersed is covered to and enters on the conductor, and coil 43 and output conductor 44 also adopt similar method then, and increases the quartz layer of protectiveness at its top.Can use usual way to connect each layer.
Sensing coil becomes the butt joint of sequence to form the gradiometer structure, and is connected to coupling liner 40,42 by conductive trace (conductive traces) 44,49, is connected to signal processing circuit by twisted-pair feeder 45.The employing twisted-pair feeder helps to reduce shifted signal or interference is picked up.
At the width of spiral coil shown in Figure 2 about 5 microns, about 10 microns of the gradient between the helical tracks.The thickness of sensing coil trace is generally about 1 micron.Each completely the diameter of coil be 0.25 millimeter.
It is relatively long and narrow that base 41 is done, and coupling liner 40,42 is relatively away from ring-like breach unshakable in one's determination, and this drift that helps to minimize welding lead 45 is picked up.Adopt metal shell 46 (Fig. 4 B) further to reduce shifted signal or interference is picked up at coupling regime.Circuit slides into groove 50 to the nearest connector of base after connecting.Metal shell comes down to a bit of drum that thicker enclosure wall is arranged, and is made of copper usually.Metal shell provides electromagnetic screen, helps mechanical treatment, but for system of the present invention not necessarily.
Another embodiment of sensing coil is referring to Fig. 5.The coil 47 of planar configuration is elongated and is rectangle.Its following range is approximately consistent with the coil of Fig. 2, and the coil width of combination also is 0.25 millimeter.The about 1-2 millimeter of loop length, coil is connected to coupling liner 52,53 by lead 48,51.
D. driving circuit
The magnetic driving circuit shown in Fig. 4 left side, comprises a pair of high electric current, high-speed exercisable amplifier 54,55.The main winding 56 of transformer provides electric power, and amplifier provides the drive current that surpasses an ampere to magnetize or drive coil 33 with the frequency of about 200KHz.The common-mode noise that driving circuit height balance minimizes in sensing loop or the coil 43,47 is picked up.Less inferior winding 57 is coupled to loop 34 along magnetizing coil, provides feedback voltage to come operational amplifier 54,55, and vibration maintains through on the amplitude and frequency adjusted.Inferior winding 57 also provides the optimization reference signal for the phase detecting circuit that describes below.
E. amplifier/phase detectors/Aristogrid
Low noise integrating device amplifier is the basis of this circuit, although use discrete component may obtain better noiseproof feature.Amplifier 61 is the transformers that are coupled to sensing coil, thereby reduces common mode noise signal, for the imbalance of eliminating magnetic conductor and sensing coil is provided convenience.Transformer coupled method is traditional, is positioned at amplifier 61, but does not draw especially in the drawings.Phase sensitive detector 62 also adopts the integrated circuit (IC) design of specific objective.The output of phase detectors is applied to low-pass filter 63, then digitizing in A/D converter 64.Converter should have high resolving power, such as 20 bit sigma-Δ converter.This converter chip has fabulous noise inhibiting ability at 60Hz and 50Hz frequency place, and this is helpful to the susceptibility that instrument farthest is provided.It can obtain from many manufacturers.
F. microcomputer
Microcomputer 65 comprises that microprocessor chip provides bidirectional serial communication to PC66 such as Motorola HCll and built-in port, by inserting the serial port of PC.It also provides the special-purpose member of communicating by letter with 22 with serial a/d converter 64 and stepping motor 16.Simple command language directly is programmed into microcomputer 65, allows PC to send order and acceptance response and data.
G. man-machine interface
PC provides the operational order of system of the present invention.It passes through a RS232 interface operational system, such as, the RS232 interface of slave microcomputer.
H. system operation
With direct and familiar relatively device, comprise the clearly round dot or the pattern of definition of the magnetic particle complex of sample, in one or more positions 11 depositions near the edge of disk 12.Tracking from PC control signal, apply voltage for stepping motor 22 and make it to rotate screw 23 and move the magnetic conductor array to sample disc 12.When near the sample position 11 at the edge of disk 12 and sensing coil 43 in the middle of ring-like breach 32 unshakable in one's determination, during 47 alignment, stepping motor 22 shuts down, and high amplitude (such as 1 ampere) high-frequency (200KHz) signal is applied to ring-like drive coil unshakable in one's determination 33.Then, thus drive stepping motor 16 rotating circular disk mobile example round dots through sensing coil from the signal of PC66.The magnetic particle sample in the breach is just encouraged in the high amplitude high frequencies magnetic field of breach 32.It is saturated to have a mind to drive ring type magnetic core, makes the magnetic field intensity of breach reach about 1000 oersteds.Magnetic particle will produce magnetic oscillation with excitation frequency, and its behavior is as the localization magnetic pole.The physical location of supposing magnetic particle arrives the sensing coil of slope-measuring device configuration very near sensing coil with regard to close-coupled from the magnetic field of sample.Because the sensing coil of slope-measuring device configuration, the output essence of the excitation field of unanimity is 0 or does not have so sensing coil is big relatively.In order to obtain the response of maximum possible, the geometric configurations of sensing coil becomes the spatial model coupling with sample.That is, sample pattern point can not be greater than about 0.25 millimeter.With the relative position of coil, response signal takes place significantly to change per sample.
Signal in the sensing coil environment that n.s. exists in that driving magnetic field is arranged is as the reference signal of signal processing of the present invention.Along with sample moves through one and another sensing coil, phase reversal 180 degree of these coil output signals as shown in Figure 6, thereby provide very strong detection technique.Induced voltage is exaggerated device 61 and amplifies, and handles through phase detectors 62.Signal is delivered to the output signal that PC is provided to PC through filtering, digitizing by microcomputer 65.Indicator 67 can be that the useful device of any type comes to provide information for the Systems Operator.It can be a visual detector, transmits information with numeral or graphics device; Also can be the photosystem of some type, or sound indicator, or the combination of these or other indicator.
Can the modulated output signal amplitude by relative sensing coil array mobile example.This allows only to refuse signal with outside input rather than because of sample itself because of system.The deltoid that is digitized into to the relative sample position of signal amplitude compares with the theoretical response curve that is stored among the PC66 that uses suitable classical curve fitting technique to obtain.The result of this operation provides in point-device magnetic sample content of having got rid of on intrinsic noise of instrument and the skew basis and has estimated.
Although described the preferred embodiments of the present invention above, other optional embodiment more of the present invention also should be mentioned that.Two kinds of cell windings have been introduced in our front, but also have some other feasible configurations.Above-mentioned magnetic conductor moves relative to sample disc, but if desired, can be configured to drive array relative to magnetic to disk and coupling stepping motor and move.Above-mentioned ring type magnetic core adopts the rectangular area, but also can adopt other shape.Number as at the sample particulate of point 11 positions of disk 12 illustrates, and 0.25 millimeter point of sample element can comprise the magnetic particle of about 10 5 microns sizes.Or the particulate of about 1200 1 micron sizes.
Claims (21)
1. device that utilizes magnetic particle detection by quantitative target particulate, magnetic particle and the combined formation magnetic coupling of target particulate composite sample, described device comprises:
A moveable base (12), sample deposits on it with definition mode;
A magnetic conductor (31,32,33) applies alternating magnetic field on sample;
Magnetic field (43) sensing element with output signal conductor (45);
Device (22,23,24,25 and 14,15,16,17) is used for moving described sample and enters magnetic field, produces operative relationship with described sensing element, and described sensing element has output signal as a result; And
Signal processor (62,64,65,66) comprises processor and analysis element, is used for the described output signal of described sensing element is carried out conversion process, and the signal of the described sample size of a pattern of indication is provided.
2. device according to claim 1, wherein said sensing element are the induction sensing coils.
3. device according to claim 2, wherein said sensing element are two sensing coils that separate.
4. device according to claim 3, wherein said sensing coil are pressed the slope-measuring device configuration and are connected.
5. device according to claim 3, wherein said sensing coil are the round-robin spiralitys.
6. device according to claim 3, the shape of wherein said sensing coil is a rectangle.
7. device according to claim 1, wherein said mobile device provides two-dimentional relative motion between described sample and described magnetic field applicator.
8. device according to claim 7, wherein said mobile device comprises:
Motor (22) and screw device (23,24,25) are used for respect to the linear shifting magnetic field of described movable pedestal bringing device; And
Electronic device (14,15,16,17) is used for moving described movable pedestal and sample in a predefined manner through magnetic field applicator.
9. device according to claim 1, wherein said magnetic conductor comprises:
Ring type magnetic core (31) on one side jagged (32);
The drive coil (33) that is wrapped on the described magnetic core but leaves a blank in described indentation, there; And
Apply the device of AC power to described drive coil.
10. device according to claim 9, further comprise the backfeed loop (34) that is coupled to described magnetic core and drive coil, the output of described backfeed loop is connected to described signal processor (62), makes described signal processor carry out self-correcting to external action.
11. device according to claim 9, wherein said sensing element (43) is assembled in sensor base (41) and extends into described breach with fixing relation.
12. device according to claim 11, wherein said sensing element are two sensing coils that separate, and are assemblied on the described sensor base, and connect into the gradiometer structure, described sensing coil is placed on described indentation, there.
13. device according to claim 1, wherein said signal processor comprises:
Be coupled to the amplifier (61) of the output terminal of described sensing element;
Be connected to described amplifier to regulate the phase sensitive detector (62) of output signal operating mode;
Output signal is converted to the analog to digital converter (64) of digital form; And
Be used for accepting described digital signal and be converted into the available form of people the calculation element (65,66,67) of control signal being provided also for described device.
14. device according to claim 8, wherein:
Described movable pedestal is a disk, is applied with the sample of a plurality of patterns on it; And
Described motor is a stepping motor, is suitable for basis from the described disk of the signal rotation of described signal processor.
15. device according to claim 12, wherein said sensor base is lengthened out, and coupling liner (40 is arranged in its adjacent end, 42) with conductor (44,49) connect, be used for from described sensing coil input/output signal, described sensing coil is assembled in the end of described sensor base, described sensor base further comprises around the conductor casing (46) of the described adjacent end of described coupling liner and described sensing base, is used for reducing shifted signal and interference is picked up.
16. the method for magnetic particle with the target particulate of formation magnetic coupling composite sample is coupled in a quantitative measurment, described method comprises the steps:
On base (12), apply at least one sample pattern (11);
Magnetic field is set up in position at predetermined proximity induction sensing coil;
Mobile example passes through magnetic field in a predefined manner, and the excitation magnetic particle is by mode profile and produce magnetic field oscillation;
The induction sensing coil is coupled in the magnetic field oscillation that magnetic particle produces;
Detect the voltage that the induction sensing coil produces; And
Measure the amplitude of described induced voltage, determine the quantity of the magnetic particle of vibration.
17. method according to claim 16, wherein, described detection step is finished by a pair of sensing coil (43) that connects into the gradiometer structure.
18. method according to claim 16, wherein, described base is rotatable disk.
19. method according to claim 18, wherein, described magnetic field is located to set up at breach (32), and the drive coil (33) that twines on it is being arranged on ring type magnetic core (31).
20. method according to claim 19 further comprises the steps:
In at least one zone of disk border, apply many groups instance model of mutual separation;
Mobile disk border enters the breach of ring-like core unshakable in one's determination; And
Rotating circular disk is so that sample passes breach.
21. method according to claim 16, wherein said magnetic field is set up at ring type magnetic core (31), drives winding (33) and is wrapped on the magnetic core, and the step of conversion is finished by signal processor, and described method further comprises the steps:
Apply the AC driving signal and set up magnetic field to drive coil;
Give signal processor (62,64,65,66) the AC driving signal feedback of drive coil; And
The mistake of using feedback signal correction signal processor to be subjected to external action and producing.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/975,569 | 1997-11-21 | ||
US08/975,569 US6046585A (en) | 1997-11-21 | 1997-11-21 | Method and apparatus for making quantitative measurements of localized accumulations of target particles having magnetic particles bound thereto |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1279764A CN1279764A (en) | 2001-01-10 |
CN1128365C true CN1128365C (en) | 2003-11-19 |
Family
ID=25523154
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN98811381A Expired - Lifetime CN1128365C (en) | 1997-11-21 | 1998-08-27 | Method and apparatus for making quantitave measurements of localized accumulations of magnetic particles |
Country Status (15)
Country | Link |
---|---|
US (2) | US6046585A (en) |
EP (1) | EP1036328B1 (en) |
JP (1) | JP3760096B2 (en) |
KR (1) | KR100389778B1 (en) |
CN (1) | CN1128365C (en) |
AT (1) | ATE280390T1 (en) |
AU (1) | AU9207998A (en) |
BR (1) | BR9815566B1 (en) |
CA (1) | CA2311301C (en) |
DE (1) | DE69827158T2 (en) |
DK (1) | DK1036328T3 (en) |
ES (1) | ES2232020T3 (en) |
HK (1) | HK1033771A1 (en) |
IL (1) | IL136211A (en) |
WO (1) | WO1999027369A1 (en) |
Families Citing this family (110)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6437563B1 (en) * | 1997-11-21 | 2002-08-20 | Quantum Design, Inc. | Method and apparatus for making measurements of accumulations of magnetically susceptible particles combined with analytes |
WO2000049407A2 (en) * | 1999-02-17 | 2000-08-24 | Kilian Hennes | Method for representing biologically activated inductance-altering particles and device for carrying out the method |
JP4171139B2 (en) * | 1999-07-21 | 2008-10-22 | 住友電気工業株式会社 | Immunoassay method and apparatus using magnetic substance labeling |
US6743639B1 (en) | 1999-10-13 | 2004-06-01 | Nve Corporation | Magnetizable bead detector |
US6875621B2 (en) * | 1999-10-13 | 2005-04-05 | Nve Corporation | Magnetizable bead detector |
JP2001147230A (en) * | 1999-11-19 | 2001-05-29 | Hitachi Software Eng Co Ltd | Biochip reading apparatus end labelled reagent |
RU2166751C1 (en) * | 2000-03-09 | 2001-05-10 | Никитин Петр Иванович | Process of analysis of mixture of biologic and/or chemical components with use of magnetic particles and device for its implementation |
US7241630B2 (en) * | 2000-04-10 | 2007-07-10 | Randox Laboratories, Ltd. | Paramagnetic particle detection |
DE10020376A1 (en) * | 2000-04-26 | 2001-11-08 | Inst Zelltechnologie E V | Dynamic markers |
US6736978B1 (en) | 2000-12-13 | 2004-05-18 | Iowa State University Research Foundation, Inc. | Method and apparatus for magnetoresistive monitoring of analytes in flow streams |
US6518747B2 (en) * | 2001-02-16 | 2003-02-11 | Quantum Design, Inc. | Method and apparatus for quantitative determination of accumulations of magnetic particles |
CN1136923C (en) * | 2001-03-13 | 2004-02-04 | 张兴东 | Magnetizer for moving magnetic field of blood magnetizing machine |
EP1469989B1 (en) * | 2002-01-02 | 2011-12-14 | Visen Medical, Inc. | Amine functionalized superparamagnetic nanoparticles for the synthesis of bioconjugates |
US8697029B2 (en) * | 2002-04-18 | 2014-04-15 | The Regents Of The University Of Michigan | Modulated physical and chemical sensors |
KR20040044336A (en) * | 2002-11-12 | 2004-05-28 | 마쯔시다덴기산교 가부시키가이샤 | Specific coupling reaction measuring method and reagent kit and specific coupling reaction measuring apparatus for use in the same |
DE10309132A1 (en) * | 2003-02-28 | 2004-11-18 | Forschungszentrum Jülich GmbH | Method and device for the selective detection of magnetic particles |
EP1617220B1 (en) | 2003-04-16 | 2009-08-05 | Sekisui Chemical Co., Ltd. | Process for producing a particle having magnetic material incorporated therein |
JP2007500347A (en) * | 2003-07-30 | 2007-01-11 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | On-chip magnetic particle sensor with improved SNR |
JP3962385B2 (en) | 2004-03-11 | 2007-08-22 | 株式会社日立製作所 | Immunoassay device and immunoassay method |
US20050239091A1 (en) * | 2004-04-23 | 2005-10-27 | Collis Matthew P | Extraction of nucleic acids using small diameter magnetically-responsive particles |
JP2005315677A (en) * | 2004-04-28 | 2005-11-10 | Canon Inc | Detector and detection method |
JP5053089B2 (en) * | 2004-08-03 | 2012-10-17 | ベクトン・ディキンソン・アンド・カンパニー | Use of magnetic materials for direct isolation of compounds and fractionation of multicomponent samples |
US7391091B2 (en) | 2004-09-29 | 2008-06-24 | Nve Corporation | Magnetic particle flow detector |
JP4669259B2 (en) * | 2004-10-15 | 2011-04-13 | 旭化成株式会社 | Test substance analyzer and quantitative method |
CN100527168C (en) * | 2004-12-14 | 2009-08-12 | 皇家飞利浦电子股份有限公司 | Method of determining a spatial distribution of magnetic particles |
US20060154260A1 (en) * | 2005-01-07 | 2006-07-13 | Barbour William M | Sample preparation methods for diagnostic analyses |
US7648844B2 (en) * | 2005-05-02 | 2010-01-19 | Bioscale, Inc. | Method and apparatus for detection of analyte using an acoustic device |
US7749445B2 (en) * | 2005-05-02 | 2010-07-06 | Bioscale, Inc. | Method and apparatus for analyzing bioprocess fluids |
US7611908B2 (en) * | 2005-05-02 | 2009-11-03 | Bioscale, Inc. | Method and apparatus for therapeutic drug monitoring using an acoustic device |
US7300631B2 (en) | 2005-05-02 | 2007-11-27 | Bioscale, Inc. | Method and apparatus for detection of analyte using a flexural plate wave device and magnetic particles |
US7405555B2 (en) * | 2005-05-27 | 2008-07-29 | Philip Morris Usa Inc. | Systems and methods for measuring local magnetic susceptibility including one or more balancing elements with a magnetic core and a coil |
JP4758713B2 (en) * | 2005-08-30 | 2011-08-31 | 旭化成株式会社 | Measuring apparatus and measuring method using magnetic sensor |
GB0522968D0 (en) | 2005-11-11 | 2005-12-21 | Popovich Milan M | Holographic illumination device |
EP1973575B1 (en) | 2005-12-22 | 2019-07-24 | Visen Medical, Inc. | Biocompatible fluorescent metal oxide nanoparticles |
JP4676361B2 (en) * | 2006-03-09 | 2011-04-27 | 株式会社日立製作所 | Magnetic immunoassay device |
US8337755B2 (en) * | 2006-03-13 | 2012-12-25 | Veridex, Llc | Operator independent programmable sample preparation and analysis system |
US8945946B2 (en) * | 2006-03-31 | 2015-02-03 | Canon Kabushiki Kaisha | Sensor element and detection method of magnetic particles using this element, and detection method of target substance |
GB0718706D0 (en) | 2007-09-25 | 2007-11-07 | Creative Physics Ltd | Method and apparatus for reducing laser speckle |
FR2900143B1 (en) | 2006-04-24 | 2010-08-13 | Alcan Packaging Capsules | CAPSULE METHOD AND CORRESPONDING CAPSULE |
FR2909169B1 (en) * | 2006-11-29 | 2009-02-06 | Billanco | DEVICE AND METHOD FOR MEASURING THE POSITION OF A MOBILE PIECE. |
EP2095091A1 (en) * | 2006-12-19 | 2009-09-02 | Koninklijke Philips Electronics N.V. | Measuring agglutination parameters |
WO2008100817A2 (en) | 2007-02-09 | 2008-08-21 | Visen Medical, Inc. | Polycyclo dyes and use thereof |
US9068977B2 (en) * | 2007-03-09 | 2015-06-30 | The Regents Of The University Of Michigan | Non-linear rotation rates of remotely driven particles and uses thereof |
US8927260B2 (en) * | 2007-03-12 | 2015-01-06 | Fabrico Technology, Inc. | Anaylte detection system using an oscillating magnetic field |
US8076161B2 (en) * | 2007-05-31 | 2011-12-13 | Canon Kabushiki Kaisha | Target substance detection kit and target substance detection method |
CA2692186C (en) * | 2007-06-29 | 2019-03-12 | Becton, Dickinson And Company | Methods for extraction and purification of components of biological samples |
WO2009007797A1 (en) * | 2007-07-09 | 2009-01-15 | Koninklijke Philips Electronics N.V. | Microelectronic sensor device with magnetic field generator and carrier |
WO2009033056A1 (en) * | 2007-09-06 | 2009-03-12 | Bioscale, Inc. | Reusable detection surfaces and methods of using same |
US7994780B2 (en) * | 2007-09-14 | 2011-08-09 | General Electric Company | System and method for inspection of parts with an eddy current probe |
EP2240776B1 (en) * | 2008-02-06 | 2014-12-24 | Koninklijke Philips N.V. | Magnetic bead actuation using feedback for ftir biosensor |
CN101603962B (en) * | 2008-06-10 | 2013-09-11 | 熊慧 | Immune nanometer magnetic bead diagnostic kit |
US11726332B2 (en) | 2009-04-27 | 2023-08-15 | Digilens Inc. | Diffractive projection apparatus |
US9335604B2 (en) | 2013-12-11 | 2016-05-10 | Milan Momcilo Popovich | Holographic waveguide display |
US10634741B2 (en) * | 2009-12-04 | 2020-04-28 | Endomagnetics Ltd. | Magnetic probe apparatus |
FI124980B (en) | 2010-01-20 | 2015-04-15 | Hemeltron | Ferromagnetic particle measurement system |
CN102770751A (en) | 2010-02-23 | 2012-11-07 | B.R.A.H.M.S有限公司 | A method for determining a marker in small volume of a sample of a bodily fluid |
DE102010009161A1 (en) | 2010-02-24 | 2011-08-25 | Technische Hochschule Mittelhessen, 35390 | Improvement of the detection limit of magnetically labeled samples |
US20110262989A1 (en) | 2010-04-21 | 2011-10-27 | Nanomr, Inc. | Isolating a target analyte from a body fluid |
WO2012011477A1 (en) * | 2010-07-21 | 2012-01-26 | 株式会社日立製作所 | Magnetic-field measurement device |
WO2012027747A2 (en) | 2010-08-27 | 2012-03-01 | The Regents Of The University Of Michigan | Asynchronous magnetic bead rotation sensing systems and methods |
US9778225B2 (en) * | 2010-11-15 | 2017-10-03 | Regents Of The University Of Minnesota | Magnetic search coil for measuring real-time brownian relaxation of magnetic nanoparticles |
WO2012136970A1 (en) | 2011-04-07 | 2012-10-11 | Milan Momcilo Popovich | Laser despeckler based on angular diversity |
US9816993B2 (en) | 2011-04-11 | 2017-11-14 | The Regents Of The University Of Michigan | Magnetically induced microspinning for super-detection and super-characterization of biomarkers and live cells |
GB2497249B (en) | 2011-07-12 | 2016-12-28 | Foodchek Systems Inc | Culture medium,method for culturing salmonella and e.coli and method for detecting salmonella and e.coli |
EP2748670B1 (en) | 2011-08-24 | 2015-11-18 | Rockwell Collins, Inc. | Wearable data display |
US10670876B2 (en) | 2011-08-24 | 2020-06-02 | Digilens Inc. | Waveguide laser illuminator incorporating a despeckler |
WO2016020630A2 (en) | 2014-08-08 | 2016-02-11 | Milan Momcilo Popovich | Waveguide laser illuminator incorporating a despeckler |
US20150010265A1 (en) | 2012-01-06 | 2015-01-08 | Milan, Momcilo POPOVICH | Contact image sensor using switchable bragg gratings |
JP6238965B2 (en) | 2012-04-25 | 2017-11-29 | ロックウェル・コリンズ・インコーポレーテッド | Holographic wide-angle display |
US9797817B2 (en) | 2012-05-03 | 2017-10-24 | The Regents Of The University Of Michigan | Multi-mode separation for target detection |
WO2013167864A1 (en) | 2012-05-11 | 2013-11-14 | Milan Momcilo Popovich | Apparatus for eye tracking |
US9933684B2 (en) * | 2012-11-16 | 2018-04-03 | Rockwell Collins, Inc. | Transparent waveguide display providing upper and lower fields of view having a specific light output aperture configuration |
US10000557B2 (en) | 2012-12-19 | 2018-06-19 | Dnae Group Holdings Limited | Methods for raising antibodies |
US8968677B2 (en) | 2013-01-22 | 2015-03-03 | Quantum Design International, Inc. | Frazil ice conjugate assay device and method |
AU2014228808C1 (en) | 2013-03-15 | 2018-12-20 | Visen Medical, Inc. | 4,4-disubstituted cyclohexyl bridged heptamethine cyanine dyes and uses thereof |
CN105073761B (en) | 2013-03-15 | 2020-10-20 | 文森医学公司 | Substituted silaxanthene cationic red to near infrared fluorescent dyes for in vitro and in vivo imaging and detection |
CN103217365B (en) * | 2013-03-29 | 2015-04-08 | 电子科技大学 | Online oil way abrasive particle monitoring device |
WO2014188149A1 (en) | 2013-05-20 | 2014-11-27 | Milan Momcilo Popovich | Holographic waveguide eye tracker |
WO2015015138A1 (en) | 2013-07-31 | 2015-02-05 | Milan Momcilo Popovich | Method and apparatus for contact image sensing |
US9983110B2 (en) | 2013-11-04 | 2018-05-29 | The Regents Of The University Of Michigan | Asynchronous magnetic bead rotation (AMBR) microviscometer for analysis of analytes |
US10359736B2 (en) | 2014-08-08 | 2019-07-23 | Digilens Inc. | Method for holographic mastering and replication |
US10241330B2 (en) | 2014-09-19 | 2019-03-26 | Digilens, Inc. | Method and apparatus for generating input images for holographic waveguide displays |
WO2016046514A1 (en) | 2014-09-26 | 2016-03-31 | LOKOVIC, Kimberly, Sun | Holographic waveguide opticaltracker |
WO2016113534A1 (en) | 2015-01-12 | 2016-07-21 | Milan Momcilo Popovich | Environmentally isolated waveguide display |
WO2016113533A2 (en) | 2015-01-12 | 2016-07-21 | Milan Momcilo Popovich | Holographic waveguide light field displays |
US10330777B2 (en) | 2015-01-20 | 2019-06-25 | Digilens Inc. | Holographic waveguide lidar |
US9632226B2 (en) | 2015-02-12 | 2017-04-25 | Digilens Inc. | Waveguide grating device |
US10459145B2 (en) | 2015-03-16 | 2019-10-29 | Digilens Inc. | Waveguide device incorporating a light pipe |
US10591756B2 (en) | 2015-03-31 | 2020-03-17 | Digilens Inc. | Method and apparatus for contact image sensing |
KR101904784B1 (en) * | 2015-09-07 | 2018-10-05 | 한국전자통신연구원 | Apparatus for detecting nonlinear magnetic paticle based on signal excitation coil and method using the same |
EP3359999A1 (en) | 2015-10-05 | 2018-08-15 | Popovich, Milan Momcilo | Waveguide display |
EP3398007A1 (en) | 2016-02-04 | 2018-11-07 | DigiLens, Inc. | Holographic waveguide optical tracker |
EP3433659A1 (en) | 2016-03-24 | 2019-01-30 | DigiLens, Inc. | Method and apparatus for providing a polarization selective holographic waveguide device |
EP3433658B1 (en) | 2016-04-11 | 2023-08-09 | DigiLens, Inc. | Holographic waveguide apparatus for structured light projection |
KR101904781B1 (en) * | 2016-10-12 | 2018-10-05 | 한국전자통신연구원 | Method for transmitting and receiving signal for signal analysis of fmmd and apparatus using the same |
US11513350B2 (en) | 2016-12-02 | 2022-11-29 | Digilens Inc. | Waveguide device with uniform output illumination |
WO2018129398A1 (en) | 2017-01-05 | 2018-07-12 | Digilens, Inc. | Wearable heads up displays |
CN116149058A (en) | 2017-10-16 | 2023-05-23 | 迪吉伦斯公司 | System and method for multiplying image resolution of pixellated display |
KR20200108030A (en) | 2018-01-08 | 2020-09-16 | 디지렌즈 인코포레이티드. | System and method for high throughput recording of holographic gratings in waveguide cells |
US10914950B2 (en) | 2018-01-08 | 2021-02-09 | Digilens Inc. | Waveguide architectures and related methods of manufacturing |
KR20200133265A (en) | 2018-03-16 | 2020-11-26 | 디지렌즈 인코포레이티드. | Holographic waveguide with integrated birefringence control and method of manufacturing the same |
WO2020023779A1 (en) | 2018-07-25 | 2020-01-30 | Digilens Inc. | Systems and methods for fabricating a multilayer optical structure |
DE102018215457A1 (en) * | 2018-09-12 | 2020-03-12 | Siemens Healthcare Gmbh | Customizable MR local coil |
CN113692544A (en) | 2019-02-15 | 2021-11-23 | 迪吉伦斯公司 | Method and apparatus for providing holographic waveguide display using integrated grating |
KR20210134763A (en) | 2019-03-12 | 2021-11-10 | 디지렌즈 인코포레이티드. | Holographic waveguide backlights and related manufacturing methods |
CN114207492A (en) | 2019-06-07 | 2022-03-18 | 迪吉伦斯公司 | Waveguide with transmission grating and reflection grating and method for producing the same |
EP4004646A4 (en) | 2019-07-29 | 2023-09-06 | Digilens Inc. | Methods and apparatus for multiplying the image resolution and field-of-view of a pixelated display |
US11442222B2 (en) | 2019-08-29 | 2022-09-13 | Digilens Inc. | Evacuated gratings and methods of manufacturing |
US11208682B2 (en) | 2019-09-13 | 2021-12-28 | Western Digital Technologies, Inc. | Enhanced optical detection for nucleic acid sequencing using thermally-dependent fluorophore tags |
US11747329B2 (en) * | 2019-11-22 | 2023-09-05 | Western Digital Technologies, Inc. | Magnetic gradient concentrator/reluctance detector for molecule detection |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4537861A (en) * | 1983-02-03 | 1985-08-27 | Elings Virgil B | Apparatus and method for homogeneous immunoassay |
GB8408529D0 (en) * | 1984-04-03 | 1984-05-16 | Health Lab Service Board | Concentration of biological particles |
JPS6390765A (en) * | 1986-10-03 | 1988-04-21 | Nippon Telegr & Teleph Corp <Ntt> | Squid immunoassay |
US4913883A (en) * | 1987-07-20 | 1990-04-03 | Hitachi, Ltd. | Particle agglutination immunoassay apparatus |
JPH0619469B2 (en) * | 1988-04-13 | 1994-03-16 | 大和製衡株式会社 | Foreign matter contamination detector such as metal |
US5001424A (en) * | 1989-02-03 | 1991-03-19 | Product Resources, Inc. | Apparatus for measuring magnetic particles suspended in a fluid based on fluctuations in an induced voltage |
TW199858B (en) | 1990-03-30 | 1993-02-11 | Fujirebio Kk | |
FR2679660B1 (en) * | 1991-07-22 | 1993-11-12 | Pasteur Diagnostics | METHOD AND MAGNETIC DEVICE FOR IMMUNOLOGICAL ANALYSIS ON A SOLID PHASE. |
US5445970A (en) * | 1992-03-20 | 1995-08-29 | Abbott Laboratories | Magnetically assisted binding assays using magnetically labeled binding members |
US5445971A (en) * | 1992-03-20 | 1995-08-29 | Abbott Laboratories | Magnetically assisted binding assays using magnetically labeled binding members |
AU686604B2 (en) * | 1993-05-17 | 1998-02-12 | Fujirebio Inc. | Method and apparatus for performing an indirect agglutination immunoassay |
US5486457A (en) * | 1993-08-25 | 1996-01-23 | Children's Medical Center Corporation | Method and system for measurement of mechanical properties of molecules and cells |
US5656429A (en) * | 1994-10-03 | 1997-08-12 | Adelman; Lonnie W. | Polynucleotide and protein analysis method using magnetizable moieties |
-
1997
- 1997-11-21 US US08/975,569 patent/US6046585A/en not_active Expired - Lifetime
-
1998
- 1998-08-27 KR KR10-2000-7005512A patent/KR100389778B1/en active IP Right Grant
- 1998-08-27 CN CN98811381A patent/CN1128365C/en not_active Expired - Lifetime
- 1998-08-27 EP EP98944568A patent/EP1036328B1/en not_active Expired - Lifetime
- 1998-08-27 JP JP2000522455A patent/JP3760096B2/en not_active Expired - Lifetime
- 1998-08-27 IL IL13621198A patent/IL136211A/en not_active IP Right Cessation
- 1998-08-27 BR BRPI9815566-0A patent/BR9815566B1/en not_active IP Right Cessation
- 1998-08-27 ES ES98944568T patent/ES2232020T3/en not_active Expired - Lifetime
- 1998-08-27 DE DE69827158T patent/DE69827158T2/en not_active Expired - Lifetime
- 1998-08-27 WO PCT/US1998/017815 patent/WO1999027369A1/en active IP Right Grant
- 1998-08-27 CA CA002311301A patent/CA2311301C/en not_active Expired - Lifetime
- 1998-08-27 DK DK98944568T patent/DK1036328T3/en active
- 1998-08-27 AU AU92079/98A patent/AU9207998A/en not_active Abandoned
- 1998-08-27 AT AT98944568T patent/ATE280390T1/en active
-
2000
- 2000-05-22 US US09/576,103 patent/US6275031B1/en not_active Expired - Lifetime
-
2001
- 2001-06-13 HK HK01104042A patent/HK1033771A1/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
CA2311301A1 (en) | 1999-06-03 |
ATE280390T1 (en) | 2004-11-15 |
BR9815566A (en) | 2000-10-31 |
KR20010032302A (en) | 2001-04-16 |
ES2232020T3 (en) | 2005-05-16 |
IL136211A0 (en) | 2001-05-20 |
DK1036328T3 (en) | 2005-01-31 |
JP2001524675A (en) | 2001-12-04 |
AU9207998A (en) | 1999-06-15 |
US6046585A (en) | 2000-04-04 |
IL136211A (en) | 2003-04-10 |
CA2311301C (en) | 2005-01-18 |
EP1036328B1 (en) | 2004-10-20 |
DE69827158D1 (en) | 2004-11-25 |
KR100389778B1 (en) | 2003-07-02 |
US6275031B1 (en) | 2001-08-14 |
JP3760096B2 (en) | 2006-03-29 |
EP1036328A1 (en) | 2000-09-20 |
HK1033771A1 (en) | 2001-09-21 |
WO1999027369A1 (en) | 1999-06-03 |
BR9815566B1 (en) | 2011-02-08 |
DE69827158T2 (en) | 2005-10-13 |
CN1279764A (en) | 2001-01-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1128365C (en) | Method and apparatus for making quantitave measurements of localized accumulations of magnetic particles | |
CN1265194C (en) | Method and apparatus for making measurements of accumulations of magnetic particles | |
CN1300598C (en) | Method and apparatus for detection and measurement of accumulations of magnetic particles | |
US8217647B2 (en) | Measuring agglutination parameters | |
Chieh et al. | Immunomagnetic reduction assay using high-Tc superconducting-quantum-interference-device-based magnetosusceptometry | |
Tsukada et al. | Using magnetic field gradients to shorten the antigen-antibody reaction time for a magnetic immunoassay | |
EP1936350A1 (en) | A method for quantitatively measuring agglutination parameters | |
EP2212686B1 (en) | Coil mechanism for magnetic detector |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CX01 | Expiry of patent term |
Granted publication date: 20031119 |
|
CX01 | Expiry of patent term |